Therapeutic evaluation of microRNA-15a and microRNA-16 in ovarian cancer. Oncotarget 2016 Mar 22;7(12):15093-104
Date
02/27/2016Pubmed ID
26918603Pubmed Central ID
PMC4924772DOI
10.18632/oncotarget.7618Scopus ID
2-s2.0-84962911774 43 CitationsAbstract
Treatment of chemo-resistant ovarian cancer (OvCa) remains clinically challenging and there is a pressing need to identify novel therapeutic strategies. Here we report that multiple mechanisms that promote OvCa progression and chemo-resistance could be inhibited by ectopic expression of miR-15a and miR-16. Significant correlations between low expression of miR-16, high expression of BMI1 and shortened overall survival (OS) were noted in high grade serous (HGS) OvCa patients upon analysis of The Cancer Genome Atlas (TCGA). Targeting BMI1, in vitro with either microRNA reduced clonal growth of OvCa cells. Additionally, epithelial to mesenchymal transition (EMT) as well as expression of the cisplatin transporter ATP7B were inhibited by miR-15a and miR-16 resulting in decreased degradation of the extra-cellular matrix and enhanced sensitization of OvCa cells to cisplatin. Nanoliposomal delivery of the miR-15a and miR-16 combination, in a pre-clinical chemo-resistant orthotopic mouse model of OvCa, demonstrated striking reduction in tumor burden compared to cisplatin alone. Thus, with the advent of miR replacement therapy some of which are in Phase 2 clinical trials, miR-15a and miR-16 represent novel ammunition in the anti-OvCa arsenal.
Author List
Dwivedi SK, Mustafi SB, Mangala LS, Jiang D, Pradeep S, Rodriguez-Aguayo C, Ling H, Ivan C, Mukherjee P, Calin GA, Lopez-Berestein G, Sood AK, Bhattacharya RAuthor
Sunila Pradeep PhD Assistant Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
Biomarkers, Tumor
Cell Movement
Cell Proliferation
Cystadenocarcinoma, Serous
Drug Resistance, Neoplasm
Epithelial-Mesenchymal Transition
Female
Gene Expression Regulation, Neoplastic
Humans
Mice
Mice, Nude
MicroRNAs
Ovarian Neoplasms
Polycomb Repressive Complex 1
Prognosis
Survival Rate
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
